White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank

Abstract Background The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK). Methods We evaluated 424 407 adults aged 37–73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006–2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference. Results There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HRQ4 = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers (ncases / n = 244 / 19 464, HRQ4 = 2.15, 95% CI = 1.46 to 3.16), former smokers (ncases / n = 280 / 69 198, HRQ4 = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (ncases / n = 108 / 111 294, HRQ4 = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (ncase s / n = 329 / 22 934, HRQ4 = 2.95, 95% CI = 2.04 to 4.26) and former smokers (ncases / n = 358/71 616, HRQ4 = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions. Conclusions Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.

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Relationships of sleep traits with lung cancer risk: a prospective cohort study in UK Biobank

SLEEP ◽

10.1093/sleep/zsab089 ◽

2021 ◽

Author(s):

Junxing Xie ◽

Meng Zhu ◽

Mengmeng Ji ◽

Jingyi Fan ◽

Yanqian Huang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Sleep Duration ◽

Genetic Risk ◽

Lung Cancer Risk ◽

Polygenic Risk Score ◽

Uk Biobank ◽

High Genetic Risk ◽

Sleep Behaviors ◽

Incident Cases

Abstract Study objectives To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer. Methods We included 469,691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable adjusted hazard ratios (HR) for lung cancer (2,177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia and snoring), and examined the interaction and joint effects with a lung cancer polygenic risk score. Results A U-shaped association was observed for sleep duration and lung cancer risk, with a 18% higher risk (95% confidence interval (CI): 1.07-1.30) for short sleepers and a 17% higher risk (95%CI: 1.02-1.34) for long sleepers compared with normal sleepers (7-8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95%CI: 1.07-1.46), but no association was found for insomnia or snoring. Compared to participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (<7 hours or >8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HRsleep duration: 1.83; 95%CI: 1.47-2.27; HRchronotype: 1.85; 95%CI: 1.34-2.56). Conclusions Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.

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Lung Cancer Risk Reduction After Smoking Cessation: Observations From a Prospective Cohort of Women

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.085 ◽

2003 ◽

Vol 21 (5) ◽

pp. 921-926 ◽

Cited By ~ 118

Author(s):

J.O. Ebbert ◽

P. Yang ◽

C.M. Vachon ◽

R.A. Vierkant ◽

J.R. Cerhan ◽

...

Keyword(s):

Lung Cancer ◽

Smoking Cessation ◽

Cancer Risk ◽

Risk Reduction ◽

Prospective Cohort ◽

Lung Cancer Risk ◽

Smoking History ◽

Cox Regression Analysis ◽

Former Smokers ◽

Never Smokers

Purpose: We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed. Methods: The Iowa Women’s Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis. Results: There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers. Conclusion: The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.

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Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative prospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1504 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1504-1504

Author(s):

Ange Wang ◽

Jessica Kubo ◽

Juhua Luo ◽

Manisha Desai ◽

Michael T Henderson ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Cancer Incidence ◽

Passive Smoking ◽

Prospective Cohort ◽

Lung Cancer Risk ◽

Lung Cancer Incidence ◽

Cancer Subtypes ◽

Former Smokers ◽

Never Smokers

1504 Background: The relationship between both active and passive smoking and lung cancer incidence in post-menopausal women was examined in theWomen’s Health Initiative Observational Study (WHI-OS). Methods: The WHI-OS, a prospective cohort study conducted at 40 U.S. centers, enrolled women ages 50-79 from 1993-1998.Among 93,676 participants, 76,304 women with complete smoking and covariate data comprised the analytic cohort, in which the association of lung cancer incidence with active and passive (childhood, adult home, and work) smoking exposure was studied. Results: Over 10.5 meanyears of follow-up with 901 lung cancer cases, lung cancer incidence was higher in current smokers (HR 13.44, 95% CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08), compared to never smokers. This relationship was dose-dependent for both current and former smokers. Risk of all lung cancer subtypes, particularly small cell lung cancer (SCLC) and squamous cell carcinoma (SqCC), was higher in smokers. Among never smokers, any passive smoking exposure (HR 0.88, 95% CI 0.52-1.49) and most passive smoking categories did not significantly increase lung cancer risk, compared to no passive exposure; however, passive exposure as an adult at home for >=30 years was associated with increased risk, of borderline significance (HR 1.61, 95% CI 1.00-2.58). Current smokers had an annualized lung cancer incidence rate of 472.9 cases/100,000 person-years, compared to 158.1 for former smokers and 36.2 for never smokers (112.3 overall). Conclusions: To our knowledge, this is the first study to examine both active and passive smoking in relation to lung cancer incidence in a complete prospective cohort of U.S. women. Active smoking is associated with significant increases in incidence of all lung cancer subtypes in post-menopausal women, particularly SCLC and SqCC. Smoking cessation decreases lung cancer risk. Prolonged exposure as an adult at home may be the strongest passive smoking contributor to lung cancer risk in this cohort. The findings support continued need for investment in smoking prevention and cessation, research on passive smoking, and understanding of lung cancer risk factors other than smoking.

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Triglyceride-Glucose Index Is Not Associated With Lung Cancer Risk: A Prospective Cohort Study in the UK Biobank

Frontiers in Oncology ◽

10.3389/fonc.2021.774937 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lijie Wang ◽

Shucheng Si ◽

Jiqing Li ◽

Yunxia Li ◽

Xiaolu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Prospective Cohort ◽

Lung Cancer Risk ◽

Cox Regression ◽

Uk Biobank ◽

Joint Effects ◽

Tyg Index ◽

The Uk ◽

The Relationship

BackgroundThe triglyceride-glucose (TyG) index is a practical substitute measure for insulin resistance (IR). The relationship between IR and lung cancer has been examined in previous studies; however, the findings have been controversial. In addition, previous studies had small sample sizes. Thus, we systematically examined the association between IR and lung cancer risk based on the UK Biobank with IR measured by the TyG index and further examined the interactions and joint effects for lung cancer.MethodsA total of 324,334 individuals free from any type of cancer at recruitment from the UK Biobank prospective cohort were included. The participants were predominantly between 40 and 70 years old. After adjusting for relevant confounders, multivariable Cox regression models were constructed to examine the relationship between the TyG index and the risk of lung cancer. We also checked the interactions and joint effects using a polygenic risk score (PRS) for lung cancer.ResultsDuring a median follow-up of 9 years, 1,593 individuals were diagnosed with lung cancer. No association was found between the TyG index and lung cancer risk after multivariate Cox regression analysis adjusted for risk factors (hazard ratio: 0.91; 95% confidence interval: 0.64–1.18). No interaction or joint effects for genetic risk and the TyG index were observed.ConclusionThe TyG index was not associated with the risk of lung cancer. Our results provide limited evidence that IR is not correlated with the risk of lung cancer.

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Cancer of the Lung, Larynx, and Pleura

10.1093/oso/9780190676827.003.0014 ◽

2018 ◽

Author(s):

Jyoti Malhotra ◽

Paolo Boffetta ◽

Lorelei Mucci

Keyword(s):

Lung Cancer ◽

Secondhand Smoke ◽

Lung Cancer Risk ◽

Occupational Exposures ◽

Men And Women ◽

Established Risk Factor ◽

Former Smokers ◽

Never Smokers ◽

Exposure To Secondhand Smoke ◽

Cancer Of The Lung

Lung cancer is the most commonly diagnosed cancer among men in most countries, and is the primary cause of cancer death in men and women. Its epidemic increase in incidence began in the first half of the twentieth century, paralleling the uptake of cigarette smoking that occurred 20 years before. A series of landmark studies beginning in 1950 established tobacco as the primary cause of lung cancer. Current smokers have a 10- to 20-fold higher lung cancer risk compared to never smokers. Important for prevention, former smokers substantially reduce this excess risk 5 years after smoking cessation. Exposure to secondhand smoke, a well-established risk factor for lung cancer, has a 20%–25% higher risk for those exposed. There are several occupational exposures associated with lung cancer, including asbestos. Despite the success in defining lung cancer’s etiology, this highly preventable disease remains among the most common and most lethal cancers globally.

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Ambient air pollution and lung cancer risk among never-smokers in the Womenʼs Health Initiative

Environmental Epidemiology ◽

10.1097/ee9.0000000000000076 ◽

2019 ◽

Vol 3 (6) ◽

pp. e076

Author(s):

Shilpa N. Gowda ◽

Anneclaire J. DeRoos ◽

Rebecca P. Hunt ◽

Amanda J. Gassett ◽

Maria C. Mirabelli ◽

...

Keyword(s):

Lung Cancer ◽

Air Pollution ◽

Cancer Risk ◽

Lung Cancer Risk ◽

Ambient Air ◽

Ambient Air Pollution ◽

Health Initiative ◽

Never Smokers

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Never smokers and lung cancer risk: A case-control study of epidemiological factors

Yearbook of Oncology ◽

10.1016/s1040-1741(08)70390-7 ◽

2007 ◽

Vol 2007 ◽

pp. 161-165

Author(s):

N.H. Hanna

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Case Control Study ◽

Lung Cancer Risk ◽

Case Control ◽

Epidemiological Factors ◽

Never Smokers ◽

Control Study

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Body mass index and lung cancer risk in never smokers: a meta-analysis

BMC Cancer ◽

10.1186/s12885-018-4543-y ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 10

Author(s):

Hongjun Zhu ◽

Shuanglin Zhang

Keyword(s):

Lung Cancer ◽

Body Mass Index ◽

Cancer Risk ◽

Body Mass ◽

Lung Cancer Risk ◽

Meta Analysis ◽

Never Smokers

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Assessment of feasibility and willingness of former heavy smokers to participate in chemoprevention trials to prevent lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21155 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21155-e21155

Author(s):

Nagi B. Kumar ◽

Gwendolyn P. Quinn ◽

Theresa Crocker ◽

Mark Alexandrow ◽

Jhanelle Elaine Gray ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Lung Cancer Risk ◽

Smoking History ◽

Cancer Center ◽

X Rays ◽

Lung Cancers ◽

Multiple Blood ◽

Former Smokers ◽

Heavy Smokers

e21155 Background: Over 50% of new lung cancers occur in former smokers, who often are seeking strategies to reduce their lung cancer risk. However, recruitment and retention of participants in chemoprevention trials continues to be costly and presents unique challenges. Evaluation of feasibility and knowledge of challenges are critical to inform design and ensure accrual in chemoprevention trials.The study assessed interest and willingness of former heavy smokers to participate in a chemoprevention clinical trial using a botanical agent to prevent lung cancer. Methods: An introductory letter and survey instrument that included the goal of the survey, epidemiological and smoking history, acceptability of trial procedures, perception of lung cancer risk and interest in participating in this trial were mailed to 500 consecutive, former heavy smokers with no cancer from a database of 826 subjects at the Moffitt Cancer Center. Results: 202 (40.4%) men and women returned completed surveys. 98% of respondents were over age 60 and 56% had an undergraduate education or higher. The average years smoked was 40.7 (SD 11.9) pack years. 76% believed there was a 50% chance or greater of developing lung cancer. In response to interest and motivation to participate, 92-96% reported interest in receiving free lung exams, health status monitoring and knowing their lung cancer risk. 88% were interested in being a part of a trial to evaluate a botanical agent for lung cancer prevention. Over 92% of subjects reported a willingness to comply with study requirements, multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about undergoing bronchoscopy, taking multiple study agents and possible assignment to a placebo arm. Conclusions: Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of former smokers to participate in chemoprevention trials.

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